Several publications and patent documents are cited throughout the specification in order to describe the state of the art to which this invention pertains. Each of these citations is incorporated herein by reference as though set forth in full.
The current treatment of hemophilia is burdened by the development of antibodies to the factor infused in the patients to treat bleeding episodes. As a bypass to this complication, one successful mode of treatment includes infusion of recombinant activated FVII (rFVIIa) that can bring about cessation of bleeding even in the presence of such inhibitory antibodies. Unfortunately, rFVIIa has a very short circulating time in humans (˜3 h) and therefore multiple injections need to be made in order to stop the bleeding. This escalates the cost of treatment tremendously and therefore development of alternative treatment strategies (either via improved proteins or gene-based therapies) is urgently needed.